ArticleProceedings of the National Academy of Sciences of the United States of America2011
Facultative role for T cells in extrafollicular Toll-like receptor-dependent autoreactive B-cell responses in vivo.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 69 citations in OpenAlex.
- Exaggerated follicular helper T-cell responses in patients with LRBA deficiency caused by failure of CTLA4-mediated regulation.The Journal of allergy and clinical immunology · 2018Trial
- Viral subversion of B-cell tolerance: mechanisms linking infection to autoimmunity.EMBO reports · 2026Review
- Multiple roads to IgE memory: A pluralistic model of IgE immunity.Cell reports · 2026Review
- Germinal-centre and extrafollicular B cell pathways in systemic lupus erythematosus.Nature reviews. Rheumatology · 2026Review
- Atypical memory B cell clonal expansion and inflammatory programs associate with platelet-activating antibody development in COVID-19.JCI insight · 2026Article
- Distributed apoptotic checkpoints in B cell selection, tolerance, and autoimmunity.Frontiers in immunology · 2026Review
- Coordinated Regulation of Extrafollicular B Cell Responses by IL-12 and IFNγ.Immunological reviews · 2025Review
- Cutting Edge: Low-dose Recombinant IL-2 Treatment Prevents Autoantibody Responses in Systemic Lupus Erythematosus via Regulatory T Cell-independent Depletion of T Follicular Helper Cells.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Failed Downregulation of PI3K Signaling Makes Autoreactive B Cells Receptive to Bystander T Cell Help.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- B cell development and antibody responses in human immune system mice: current status and future perspective.Science China. Life sciences · 2024Review
- T cell help shapes B cell tolerance.Science immunology · 2024Article
- Antigen presentation by B cells enables epitope spreading across an MHC barrier.Nature communications · 2023Article
- T cell help in the autoreactive germinal center.Scandinavian journal of immunology · 2022Review
- Proteogenomic analysis of the autoreactive B cell repertoire in blood and tissues of patients with Sjögren's syndrome.Annals of the rheumatic diseases · 2022Article
- The extrafollicular response is sufficient to drive initiation of autoimmunity and early disease hallmarks of lupus.Frontiers in immunology · 2022Article
- TLR7 Activation Accelerates Cardiovascular Pathology in a Mouse Model of Lupus.Frontiers in immunology · 2022Article
- Follicular T cells are clonally and transcriptionally distinct in B cell-driven mouse autoimmune disease.Nature communications · 2021Article
- Cutting Edge: A Threshold of B Cell Costimulatory Signals Is Required for Spontaneous Germinal Center Formation in Autoimmunity.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- BCR Affinity Influences T-B Interactions and B Cell Development in Secondary Lymphoid Organs.Frontiers in immunology · 2021Review
- The T-cell response to SARS-CoV-2: kinetic and quantitative aspects and the case for their protective role.Oxford open immunology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Extrafollicular (EF) B-cell responses are increasingly being recognized as an alternative pathway of B-cell activation, particularly in autoimmunity. Critical cellular interactions required for the EF B-cell response are unclear. A key question in autoimmunity, in which Toll-like receptor (TLR) signals are costimulatory and could be sufficient for B-cell activation, is whether T cells are required for the response. This is pivotal, because autoreactive B cells are considered antigen-presenting cells for autoreactive T cells, but where such interactions occur has not been identified. Here, using AM14 site-directed transgenic rheumatoid factor (RF) mice, we report that B cells can be activated, differentiate, and isotype-switch independent of antigen-specific T-cell help, αβ T cells, CD40L signaling, and IL-21 signaling to B cells. However, T cells do dramatically enhance the response, and this occurs via CD40L and IL-21 signals. Surprisingly, the response is completely inducible T-cell costimulator ligand independent. These results establish that, although not required, T cells substantially amplify EF autoantibody production and thereby implicate T-independent autoreactive B cells as a potential vector for breaking T-cell tolerance. We suggest that these findings explain why autoreactivity first focuses on self-components for which B cells carry TLR ligands, because these will uniquely be able to activate B cells independently of T cells, with subsequent T-B interactions activating autoreactive T cells, resulting in chronic autoimmunity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.